The abuse of psychomotor stimulants such as cocaine and methamphetamine is a continuing and very serious problem. In our program to synthesize and evaluate a number of 5-HT agonists and their antagonists, we recently developed a practical nonchromatographic chemical synthesis of the 5-HT2A receptor antagonist MDL100,907 that is providing multigram amounts of this critical research tool. We have also studied the discriminative stimulus effects of MDL100,907 several other drugs in order to gain further insight into their 5-HT receptor subtype(s) selectivity and the possible receptor role in certain neuropsychiatric disorders. Our studies show that in rats, DOM and MDL100907 discriminative stimulus effects are mediated by 5-HT2A receptors and that ketanserin discriminative stimulus effects involve both 5-HT2A and alpha1 adrenergic receptors. Results in 5-HT depleted rats further suggest that the discriminative stimulus effects of MDL100907 might involve antagonism of endogenous 5-HT and/or inverse agonism at 5-HT2A receptors.